Autism and vitamin D evidence - Cannell Feb 2016

Vitamin-D and Autism Spectrum Disorder (ASD): prevention and treatment. , John Cannell

Context. Autism Spectrum Disorder [ASD], a common neurodevelopmental disorder characterized by impaired communication, and repetitive behaviours, diagnosed in 1 in every 64 eight-year-old American children, has recently shown dramatically increased incidence, possibly reflecting increased surveillance, over-diagnosis, or being a true increase in incidence.

Evidence acquisition, from the relevant peer-reviewed literature [1960's-2016 (PubMed)].

Evidence synthesis. Data collation on hypovitaminosis-D effects on neural function, and of effects of high-dosage vitamin D, including two randomized controlled trials (RCT) in autistic children.
Mechanisms. Possible mechanisms of action of vitamin D in preventing and treating ASD are well known, as recently [and repeatedly] reviewed, reducing risk or severity through anti-inflammatory effects, DNA repair mechanisms, anti-autoimmune effects, raising seizure threshold, increasing T-regulatory cells, protecting mitochondria, and up-regulating glutathione, which scavenges oxidative by-products and clears heavy metals [by chelation].

Epidemiological data. Recent meta-analysis [11 cross-sectional studies] reported vitamin D deficiency was much more common in children with ASD than in controls.[ Wang T, Shan L, Du L, Feng J, Xu Z, Staal WG, Jia F. Serum concentration of 25-hydroxyvitamin D in autism spectrum disorder: a systematic review and meta-analysis. Eur Child Adolesc Psychiatry. 2015 Oct 29
] Another study found that new-borns who later developed autism had lower vitamin D levels at birth than their healthy siblings, suggesting that the vitamin D system is involved in ASD genetics.[ Fernell E, Bejerot S, Westerlund J, Miniscalco C, Simila H, Eyles D, Gillberg C, Humble MB. Autism spectrum disorder and low vitamin D at birth: a sibling control study. Fernell E, Bejerot S, Westerlund J, Miniscalco C, Simila H, Eyles D, Gillberg C, Humble MB. Mol Autism. 2015 Jan 14;6:3.]

Human interventional studies Only two RCTs [of high-dose vitamin D (300 IU/kg/day) are reported; both finding significant improvement in ~75% of supplemented ASD children.[[ Feng J, Shan L, Du L, Wang B, Li H, Wang W, Wang T, Dong H, Yue X, Xu Z, Staal WG, Jia F. Clinical improvement following vitamin D3 supplementation in Autism Spectrum Disorder. Nutr Neurosci. 2016 Jan 18.], [ Randomized-Controlled Trial of Vitamin D Supplementation in Children with Autism Spectrum Disorder: (In submission) Clinical Trial. Trial registration number: UMIN-CTR Study Design: trial Number: UMIN000020281.]
An open study of infants born to mothers who already had one child with ASD, found vitamin D given to pregnant women and young children reduced subsequent ASD incidence to 5% instead of the 20% consistently reported for such infants in the literature.[ Stubbs G, Henley K, Green J. Autism: Will vitamin D supplementation during pregnancy and early childhood reduce the recurrence rate of autism in newborn siblings? Med Hypotheses. 2016 Mar;88:74-8.]

Conclusions.
High-dose vitamin D administration appears to improve core features of ASD, through well described actions of vitamin D on the central nervous system. Future RCTs of vitamin D in ASD may fail if lower doses are used, if subjects are sufficient at baseline, if placebo controls are treated, if pre/post RCT 25(OH)D levels are not done, and if ASD rating scales are not used.

Overall, therefore, we recommend avoidance of hypovitaminosis D in pregnancy and childhood by supplementing all pregnant women, infants and toddlers with adequate amounts of vitamin D [[see Section XX].

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See also Vitamin D Life

• Autism rate in siblings reduced 4X by vitamin D: 5,000 IU during pregnancy, 1,000 IU to infants – Feb 2016 - referenced above
• Autism is associated with low vitamin D – meta-analysis Oct 2015
• Autism treated by Vitamin D: Dr. Cannell - video June 2013 includes many reasons why he believes Autism is related to Vitamin D

1. Both have strong inheritance features – Vitamin D about 60%
2. Both have gotten substantially worse in last 30 years
3. Vitamin D is known to be involved in brain development
4. All autistic children are VitD deficient, but not all children who are deficient are autistic: genes are involved
5. When giving vitamin D to cure children of rickets “mental dullness” decreases as well
6. Children with genes which give them too much (Williams Syndrome) have to reverse of autism – too sociable
7. Mothers having lots of fish (and thus more vitamin D) give birth to kids with less autistic symptoms
8. Both associated with weak bones
9. Both worse around the age of weaning
10. Autism is more common in rich families – more likely to apply sun screen and stay indoors
11. Autism increases with drugs which lower levels of vitamin D
12. Seizures are common with Autism - Vitamin D has been shown to reduce seizures
13. Fewer autistic symptoms (such as sleep problems) during summer: when child gets more vitamin D from the sun
14. Both worse with latitude
15. Both vary with Ultraviolet light
16. Both vary with time of year (more birth of autistics in March in Northern hemisphere)
17. 2X more urban autism – less UVB in urban environments
18. Both worse with pollution
19. Both worse with increased clouds and rain
20. Both worse with closely spaced pregnancies
21. Autistics have abnormal immune response – similar to that of vitamin D deficiency
22. Low levels of vitamin D in mother animals reduces brain function in offspring
23. Vitamin deficient rat pups have similar brain abnormalities to that of human autistic children
24. Autistic children get less vitamin D in their blood for the same amount of sun exposure
25. The 4 males/1 female ratio - Note estrogen increases vitamin D in the brain (testosterone does not)
26. Both worse in African Americans (A-A 2-3 increased autism rate)
27. Both worse in Dark-skinned immigrants in Europe

•    Note: All articles in Autism category 133 items